The Cellular Feast: The Remarkable Power of the FGF Family Growth Factors

Introduction to the FGF Family

The FGF family, also known as the Fibroblast Growth Factor family, comprises a group of proteins that play a crucial regulatory role in cell growth, development, and differentiation. These growth factors are widely distributed in the human body and exert stimulatory or inhibitory effects on various cell types. Members of the FGF family function during the earliest stages of embryonic development and organogenesis, maintaining progenitor cells and mediating their growth, differentiation, survival, and patterning. In adult tissues, FGFs also play roles, often by reactivating developmental signaling pathways to mediate metabolic functions, tissue repair, and regeneration.

Source: DOI: 10.1002/wdev.176

Phylogenetic analysis reveals that the 22 Fgf genes can be divided into 7 subfamilies, each containing 2 to 4 members. The branch lengths are proportional to the evolutionary distance between each gene. The Fgf1, Fgf4, Fgf7, Fgf8, and Fgf9 subfamily genes encode secreted canonical FGFs, which bind to heparin/heparan sulfate (HS) as cofactors and activate FGFRs. The Fgf15/19 subfamily members encode endocrine FGFs, which bind to Klotho family proteins as cofactors and activate FGFRs. The Fgf11 subfamily genes encode intracellular FGFs, which are non-signaling proteins acting as cofactors for voltage-gated sodium channels and other molecules.

A schematic diagram of the FGFR protein structure is shown. FGFRs are receptor tyrosine kinases of approximately 800 amino acids, featuring multiple domains, including three extracellular immunoglobulin-like domains (I, II, and III), a transmembrane domain (TM), and two intracellular tyrosine kinase domains (TK1 and TK2). SP denotes a cleavable secretory signal sequence. The Fgfr gene family consists of four members: Fgfr1-Fgfr4. Among these, Fgfr1-Fgfr3 produce two major splice variants of the immunoglobulin-like domain III, known as IIIb and IIIc, which are critical determinants of ligand-binding specificity.

 A schematic diagram of the FGFRL1/FGFR5 protein structure is shown. FGFRL1 is structurally similar to FGFRs and is a membrane protein of approximately 500 amino acids, featuring three extracellular immunoglobulin-like domains (I, II, and III), a transmembrane domain (TM), and a short intracellular tail lacking tyrosine kinase domains. SP denotes a cleavable secretory signal sequence.

Cell Types and Functions of Different FGF Subtypes

Note: The table above summarizes the common applications and functions of FGF1 to FGF23 in cell culture. Specific conditions and effects may vary depending on experimental design and cell type. Researchers should adjust protocols based on specific requirements.

Summary and Outlook

The growth factors of the FGF family hold broad application prospects in the field of cell culture. They play pivotal roles in the cultivation of stem cells, organoids, and other advanced models. With further research into the FGF family, we anticipate discovering additional members with significant value, thereby advancing cell culture technologies and their applications. In the future, FGF family growth factors are expected to play an even greater role in tissue engineering, drug development, regenerative medicine, and other fields, contributing significantly to improving human health and quality of life.

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