Receptor tyrosine kinases (RTK)s are the high-affinity cell surface receptors for many polypeptide Growth factors, Cytokines, and Hormones. Of the 90 unique tyrosine kinase genes identified in the Human genome, 58 encode receptor tyrosine kinase proteins. Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of Cancer. (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase)

Growth factor가 이곳에 결합하면, 인산화와 함께 RAS가 활성화되고 이로 인해

1. MAPK가 활성화되어 특정 transcription을 개시한다. MYC와 D cyclin 활성.
2. PI3K가 활성화되고 Akt, mTOR로 단백질 합성이 많아진다. (PTEN은 이를 저해함)

Cancer에서는 growth factor 없이도 이 경로가 활성화됨.

1. ERBB1 encodes EGFR, it mutations -> activation of EGFR tyrosine kinase
2. ERBB2 encodes HER2, it amplified in Breast cancer
3. Gene rearrangements activate other receptor tyrosine kinases, ALK. chr. 5 deletion fuses part of the ALK and EML4 -> constitutive tyrosine kinase activity

Downstream

1. RAS, GAP
2. BRAF, PI3K

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